The present invention relates to a novel peptide extract which has antimetalloprotease activity, in particular anticollagenase and antigelatinase activity. It also relates to the pharmaceutical, cosmetic or nutraceutical compositions comprising such an extract, in particular to a pharmaceutical composition intended to treat inflammatory diseases, such as arthrosis, parodontosis or ulcers, or to the cosmetic compositions intended to combat aging, which may or may not be actinic aging, or aging accelerated by outside attacks (tobacco, pollution, etc.).
The pharmaceutical, cosmetic or nutraceutical composition is also intended to treat neoangiogenesis (vessel proliferation) which is pathological or unsightly (psoriasis, tumors, erythosis, acne erythematosa, rosacea, local treatment with irritants such as retanoic acid), cicatrization deficiencies, burns or the attack of dental enamel (Ch. M. Lapiere, Cours de biologie de la peau [Skin biology course]—COBIP INSERM U 346, Lyon 1999).
Metalloproteases are a family of zinc- and calcium-dependent endopeptidases which have the combined property of degrading the diverse components of connective tissue matrices (thesis by S. Charvat—Métalloprotéinases et épiderme [Metalloproteinases and epidermis], pages 101–113 No. 248–98, 1998, Lyon I).
They are classified according to the nature of their substrate: collagenase (fibrillar collagen: ex. MMP-1, -13, -8); gelatinase (denaturated collagen, gelatin: ex. MMP-2, MMP-9); stromelysins (fibronectin, proteoglycin: ex. MMP-3, MMP-10). They are used in the physiological remodeling (low expression) or pathological remodeling of the extracellular matrix (strong induction).
Metalloproteases are in particular involved in the cicatrization process, eliminating the damaged tissues.
MMPs may act anarchically and cause significant lesions if their activity is not controlled.
Moreover, it is known that metalloproteases are involved in certain biological disorders, such as inflammatory diseases, in particular arthrosis and parodontosis (H. BIRKEDAL-HANSEN et al., Critical Reviews in Oral Biology and Medicine, 4(2): 197: 250 (1993)), in the processes of aging, in particular linked to the action of solar radiation (MARTIN RIEGER; Allured's Cosmetics & Toiletries®, Vol. 114, No. 1/January 1999 or G. J. FISHER et al., The New England Journal of Medicine, Vol. 337, No. 20 pp. 1419–1428, “Pathophysiology of premature skin aging induced by ultraviolet light” and G. J. FISHER et al., the Society for Investigative Dermatology, Inc. 1998, pp. 61–68 “Molecular mechanisms of photoaging and its prevention by retinoic acid: ultraviolet irradiation induces MAP kinase signal transduction cascades that induce A-1-regulated matrix metalloproteinases that degrade human skin in vivo”) or in acute and chronic inflammations (XIE et al.; J. Biol. Chem. 273: pp. 11576–11582; 1998) and blistering diseases (toxic epidermal necrolysis), pathologies with cellular hyperproliferation during inflammation or irritation, bedsores, burns and ulcers.
The same is true for the proliferation of neoangiogenesis endothelial cells which, in their proliferative phase during inflammatory or pathological processes (psoriasis, tumors) need MPPs to destroy the connective tissue, in order to migrate toward other regions and to form microtubules and capillaries (Controlling the vasculature: angiogenesis, anti-angiogenesis and vascular targeting of gene therapy—T. P. D. FAN, R. JAGGAR and R. BICKNELL, TiPS—February 1995, Vol. 16; Natural Products as angiogenesis inhibitors, D. H. PAPER, Planta Medical 64 (1998) pp. 686–695; Membrane-type matrix metalloproteinases in human dermal microvascular endothelial cells: expression and morphogenetic correlation—V. T. CHAN et al., J.I.D. 111, pp. 1153–1159, 1998; Matrix metalloproteinases in blood vessel development in human fetal skin and in cutaneous tumors—T. V. KARELINA et al. J.I.D.; 105, 411–417, 1995; Vascular profiferation and angiogenic factors in psoriasis, J. D. CREAMER and J. N. W. N. BARKER, Clinical and Experimental Dermatology, 1995, 20, pp. 6–9).
The role of inhibitors of metalloproteases, in particular of collagenases, gelatinases and of stromelysins, in certain treatments for the abovementioned diseases is also known.